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1.
Adv Healthc Mater ; : e2401466, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39087398

RESUMO

Aortic dissection (AD) is a severe cardiovascular disease necessitating active therapeutic strategies for early intervention and prevention. Nucleic acid drugs, known for their potent molecule-targeting therapeutic properties, offer potential for genetic suppression of AD. Piwi-interacting RNAs, a class of small RNAs, hold promise for managing cardiovascular diseases. Limited research on these RNAs and AD exists. This study demonstrates that an antagomir targeting heart-apoptosis-associated piRNA (HAAPIR) effectively regulates vascular remodeling, mitigating AD occurrence and progression through the myocyte enhancer factor 2D (Mef2D) and matrix metallopeptidase 9 (MMP9) pathways. Green tea-derived plant exosome-like nanovesicles (PELNs) are used for oral administration of antagomir. The antagomir-HAAPIR-nanovesicle complex, after purification and optimization, exhibits a high packing rate, while the antagomir is resistant to enzyme digestion. Administered to mice, the complex targets the aortic lesion, reducing AD incidence and improving survival. Moreover, MMP9 and Mef2D expression decrease significantly, inhibiting the phenotypic conversion of human aortic smooth muscle cells. PELNs encapsulate the antagomir-HAAPIR complex, maintaining stability, mediating transport into the bloodstream, and delivering Piwi-interacting RNAs to AD sites. Thus, HAAPIR is a potential target for persistent clinical AD prevention and treatment, and nanovesicle-encapsulated nucleic acids offer a promising cardiovascular disease treatment, providing insights for other therapeutic targets.

2.
Phys Chem Chem Phys ; 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39169824

RESUMO

For planar and rigid π-conjugated molecular systems, electrostatic and inductive interactions are pivotal in governing molecular packing structures and electron polarization energies. These electrostatic interactions typically exhibit an anisotropic nature within π-conjugated systems. In this study, we utilize the atoms in molecules (AIM) theory in conjunction with linear response theory to decompose molecular polarizability into distributed atomic polarizability tensors. On the basis of atomic polarizability tensors, we extended an anisotropic polarizable model into the AMOEBA polarizable force field. Both anisotropic and isotropic polarizable models in combination with various density functional theory (DFT)-derived atomic multipoles were applied to optimize the experimental crystals of naphthalene and anthracene. Furthermore, these two types of electrostatic models, coupled with the evolutionary algorithm USPEX program, are utilized to predict the crystal structures of oligoacenes. Our findings demonstrate that the anisotropic polarizable model exhibits superior performance in crystal refinement and crystal structure prediction. This enriched anisotropic polarizable model is seamlessly integrated into the AMOEBA polarizable force field and readily applicable within our modified Tinker program.

3.
Mar Environ Res ; 201: 106677, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39146806

RESUMO

To unravel the effects of environmental factors on fishery resources in the bay, we conducted six biological and environmental surveys in the Laizhou Bay between 2013 and 2020. The findings of our study illuminated several key aspects: (1) The annual discharge of water and sediment from the Yellow River to Laizhou Bay exhibited notable variations, while concurrently, environmental factors including temperature, salinity, and suspended particle matter underwent fluctuations, yet remained within a relatively stable range overall. (2) A total of 8318 eggs and larvae belonging to 10 orders, 16 families, and 19 genera were collected. Significant interannual fluctuations had been documented in the species composition, abundance, and biodiversity of ichthyoplankton. Notably, both Shannon-Wiener diversity index and Pielou evenness index were significantly negatively correlated with suspended particle matter concentration. (3) The water and sediment discharge significantly positively correlated with the number of cold-temperature species. However, the sediment input negatively correlated with the number of continental shelf benthopelagic fish. (4) Redundancy and correlation analyses confirmed the strong link between spatial and temporal distribution of fish communities and environmental factors, with salinity and dissolved oxygen key for ichthyoplankton abundance. Our research offers a scientific foundation for targeted fishery protection and management, which is crucial for preserving the ecological functions of spawning grounds in the bay.

4.
Photodiagnosis Photodyn Ther ; 49: 104305, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-39134251

RESUMO

PURPOSE: To evaluate temporal vascular arcade angle and its influencing factors in myopic children. METHODS: It was a retrospective study, we reviewed the records of 119 patients aged 6-10 years with myopia (spherical equivalent refractive error (SER) ≤ -0.05D) in the third year of follow-up in Beijing Hyperopia Reserve Research. We measured temporal vascular arcade angles on the fundus photographs and measured 3-year rate of spherical equivalent(D/year) and axial length (AXL) changes(mm/year). RESULTS: Mean age at initial visit was 7.71±1.20 years and mean SER was -1.32±1.09D. Children were divided into two groups according to the refractive status of children at baseline: Myopia onset group (SER>-0.50D at baseline) (n = 107) and Myopia progression group (SER≤-0.50D at baseline) (n = 12). The mean SER in Myopia progression group was much smaller than Myopia onset group (P < 0.001) and mean AXL in Myopia progression group was much longer than Myopia onset group (P = 0.042). AXL (r=-0.320, P < 0.001), SER change rate (r=-0.209, P = 0.022) and AXL change rate (r=-0.232, P = 0.011) were associated with temporal vascular arcade angle in all participants. In Myopia onset group, AXL (r=-0.317, P < 0.001) and AXL change rate (r=-0.190, P = 0.05) were associated with temporal vascular arcade angle. There were no parameters were associated with temporal vascular arcade angle (all P > 0.05) in Myopia progression group. Only AXL (r=-0.306, P = 0.018) was associated with temporal vascular arcade angle in girls while AXL (r=-0.370, P = 0.004), SER change rate (r=-0.317, P = 0.013) and AXL change rate (r=-0.365, P = 0.004) were all associated with the Angle in boys. CONCLUSION: Temporal vascular arcade angle was associated with the rate of SER and AXL changes in myopia onset children, and showed gender differences. These may suggest that lamina cribrosa location has different influencing factors in different genders and different stages of myopia development. Due to the small number of people in Myopia progression group, large sample size studies are still needed in the future.

5.
Artigo em Inglês | MEDLINE | ID: mdl-39178378

RESUMO

Optical camouflage offers an effective strategy for enhancing the survival chances of underwater flexible electronic devices akin to underwater organisms. Photochromism is one of the most effective methods to achieve optical camouflage. In this study, antiswelling hydrogels with photochromic properties were prepared using a two-step solvent replacement strategy and explored as underwater optically camouflaged flexible electronic devices. The hydrophobic network formed upon polymerization of hydroxyethyl methacrylate (HEMA) ensured that the hydrogels possessed outstanding antiswelling properties. Internetwork hydrogen bonding interactions allowed the hydrogels to exhibit tissue-adaptable mechanical properties and excellent self-bonding capabilities. The introduction of polyoxometalates further enhanced the hydrogels' mechanical and self-bonding properties while imparting photochromic capability. The hydrogels could be rapidly and reversibly colored under 365 nm UV irradiation. The bleaching rate of the colored hydrogels increased with temperature, bleaching within 12 h at 60 °C but maintaining the color for more than 5 days at room temperature. The self-bonding and photochromic properties enabled the hydrogels to be easily assembled into optically camouflaged underwater flexible electronic devices for underwater motion sensing and wireless information transmission. An optically camouflaged strain sensor was first assembled for underwater limb motion sensing. Additionally, an underwater optically camouflaged wireless information exchange device was assembled to enable wireless communication with a smartphone. This work provided an effective strategy for the optical camouflage of underwater flexible electronic devices, presenting opportunities for next-generation underwater hydrogel-based flexible devices.

6.
Photodiagnosis Photodyn Ther ; : 104322, 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39187225

RESUMO

PURPOSE: To evaluate the occurrence and influencing factors of myopia occurrence in pre-myopia children aged 3-6 years. METHODS: This study included 204 pre-myopia (-0.50D-0.50D). The length of macular BM was shorter in Myopia group than that in Non-myopia group (P<0.001). Baseline SE and the length of macular BM were independent influencing factors which associated with myopia occurrence (OR, 0.031; 95% CI, 0.008-0.117, P<0.001 and OR, 0.204; 95% CI, 0.055-0.763, P=0.018, respectively) by multivariate binary logistic regression analysis. SE changes process represents the changes of SE, Myopia group had the bigger SE changes (P<0.001). And in the multivariate liner regression analysis, age was the common influencing factor of SE changes process in total participants, Non-myopia group and Myopia group (B=0.244, P<0.001; B=0.078, P=0.010; B=0.161, P=0.046, respectively) CONCLUSIONS: Initial SE and the length of macular BM in pre-myopia children aged 3-6 years were the independent factors of the occurrence of myopia. And initial age was the common factor that associated with SE changes process.

8.
Anim Reprod Sci ; 268: 107534, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39047429

RESUMO

The spatiotemporal transcription of follicle-stimulating hormone receptor (FSHR) and luteinizing hormone/human chorionic gonadotropin receptor (LHCGR) are crucial events for follicular development. However, their regulatory mechanisms are unclear. DNA methylation and histone acetylation are the main epigenetic modifications, and play important roles in transcriptional expression, which regulate cell responses including cell proliferation, senescence and apoptosis. This review will discuss the dynamic epigenetic modifications of FSHR and LHCGR that occur during the process of follicular development and their response to gonadotropins. In addition, some alteration patterns that occur during these epigenetic modifications, as well as their retrospect retrotransposons, which regulate the gene expression levels of FSHR and LHCGR will be discussed.


Assuntos
Epigênese Genética , Animais , Folículo Ovariano/metabolismo , Folículo Ovariano/fisiologia , Feminino , Humanos , Receptores da Gonadotropina/genética , Receptores da Gonadotropina/metabolismo , Receptores do LH/genética , Receptores do LH/metabolismo , Receptores do FSH/genética , Receptores do FSH/metabolismo
9.
BMC Geriatr ; 24(1): 603, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009979

RESUMO

BACKGROUND: High-grade endometrial stromal sarcoma (HG-ESS) is a rare malignant tumor with poor prognosis. To overcome the limitations of current treatment for advanced patients, the intervention of targeted drug therapy is urgently needed. CASE PRESENTATION: A 74-year-old married woman who presented with abdominal distension and lower abdominal pain was admitted to Hebei General Hospital. After surgery, immunohistochemical staining revealed a malignant tumor which was consistent with HG-ESS. Tumor recurrence occurred 2 months after surgery. Then the patient underwent chemotherapy with two courses but responded poorly. Subsequently we observed ATM, BLM, and CDH1 co-mutations by Next Generation Sequencing (NGS). Then the patient received pamiparib, which resulted in a 10-month progression-free survival (PFS) and is now stable with the administration of sintilimab in combination with pamiparib and anlotinib. CONCLUSIONS: Due to the successful use of poly ADP-ribose polymerase inhibitor (PARPi) on HG-ESS, we suggest that the selection of effective targeted drugs combined with anti- programmed death-1 (PD-1) drug therapy based on genetic testing may become a new option for the treatment of homologous repair deficient (HR-deficient) HG-ESS.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia , Caderinas , Neoplasias do Endométrio , RecQ Helicases , Sarcoma do Estroma Endometrial , Humanos , Feminino , Idoso , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/patologia , Sarcoma do Estroma Endometrial/genética , Sarcoma do Estroma Endometrial/tratamento farmacológico , Sarcoma do Estroma Endometrial/diagnóstico , Proteínas Mutadas de Ataxia Telangiectasia/genética , RecQ Helicases/genética , Caderinas/genética , Antígenos CD/genética , Mutação
10.
J Gastrointest Cancer ; 55(3): 1388-1400, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39080229

RESUMO

PURPOSE: Our study aimed to evaluate the impact of concomitant medications on the response and survival of patients with advanced digestive tract cancer receiving an immunotherapy-antiangiogenesis combination. METHODS: We conducted a three-center observational retrospective study of patients with advanced digestive tract cancer who received programmed death-1 (PD-1) inhibitors plus antiangiogenic agents between March 2019 and July 2022 in China. The patients had one of the three types of primary tumors: hepatocellular carcinoma (HCC), colorectal cancer (CRC), and gastric cancer (GC). RESULTS: The study included 352 patients. The most frequently prescribed co-medications were nonsteroidal anti-inflammatory drugs (NSAIDs) (46.3%), proton pump inhibitors (PPIs) (38.0%), systemic antibiotics (33.8%), and corticosteroids (30.1%). Probiotics had a direct correlation with a higher objective response rate (ORR) (OR 2.4, 95% CI 1.2 to 4.7, p = 0.013). Patients who received PPIs for gastritis/gastroesophageal reflux disease (GERD) (HR 0.7, 95% CI 0.5 to 1.0, p = 0.045), anticoagulants (HR 0.5, 95% CI 0.3 to 0.9, p = 0.009), and probiotics (HR 0.7, 95% CI 0.5 to 1.0, p = 0.034) had longer progression-free survival (PFS). Patients who received PPIs for gastritis/GERD (HR 0.6, 95% CI 0.4 to 0.9; p = 0.009) had longer overall survival (OS), while patients receiving opioids (HR 1.5, 95% CI 1.1 to 2.0, p = 0.010) had a significantly higher risk of death. CONCLUSION: Patients with advanced digestive tract cancer who were administered PPIs for gastritis/GERD indication, anticoagulants, or probiotics in combination with PD-1 inhibitors and antiangiogenic agents experienced improved clinical outcomes. However, opioid administration was linked to reduced OS in patients receiving combined therapy.


Assuntos
Inibidores da Angiogênese , Inibidores de Checkpoint Imunológico , Humanos , Masculino , Feminino , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/administração & dosagem , Pessoa de Meia-Idade , Inibidores de Checkpoint Imunológico/uso terapêutico , Estudos Retrospectivos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adulto , Inibidores da Bomba de Prótons/uso terapêutico , Resultado do Tratamento , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Idoso de 80 Anos ou mais
11.
Plant Physiol ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38889048

RESUMO

Transcriptional reprogramming is critical for plant immunity. Several calmodulin (CaM)-binding protein 60 (CBP60) family transcription factors (TFs) in Arabidopsis (Arabidopsis thaliana), including CBP60g, Systemic Acquired Resistance Deficient 1 (SARD1), CBP60a, and CBP60b, are critical for and show distinct roles in immunity. However, there are additional CBP60 members whose function is unclear. We report here that Arabidopsis CBP60c-f, four uncharacterized CBP60 members, play redundant roles with CBP60b in the transcriptional regulation of immunity responses, whose pCBP60b-driven expression compensates the loss of CBP60b. By contrast, neither CBP60g nor SARD1 is inter-changeable with CBP60b, suggesting clade-specific functionalization. We further show that function of CBP60b clade TFs relies on DNA-binding domains (DBDs) and CaM-binding domains, suggesting that they are downstream components of calcium signaling. Importantly, we demonstrate that CBP60s encoded in earliest land plant lineage Physcomitrium patens and Selaginella moellendorffii, are functionally homologous to Arabidopsis CBP60b, suggesting that the CBP60b clade contains the prototype TFs of the CBP60 family. Furthermore, tomato and cucumber CBP60b-like genes rescue the defects of Arabidopsis cbp60b and activate the expression of tomato and cucumber SALICYLIC ACID INDUCTION DEFICIIENT2 (SID2) and ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1) genes, suggesting that immune response pathways centered on CBP60b are also evolutionarily conserved. Together, these findings suggest CBP60b clade transcription factors are functionally conserved in evolution and positively mediate immunity.

12.
Int Immunopharmacol ; 138: 112452, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-38943972

RESUMO

Peripheral nerve injury seriously endangers human life and health, but there is no clinical drug for the treatment of peripheral nerve injury, so it is imperative to develop drugs to promote the repair of peripheral nerve injury. Erythropoietin (EPO) not only has the traditional role of promoting erythropoiesis, but also has a tissue-protective effect. Over the past few decades, researchers have confirmed that EPO has neuroprotective effects. However, side effects caused by long-term use of EPO limited its clinical application. Therefore, EPO derivatives with low side effects have been explored. Among them, ARA290 has shown significant protective effects on the nervous system, but the biggest disadvantage of ARA290, its short half-life, limits its application. To address the short half-life issue, the researchers modified ARA290 with thioether cyclization to generate a thioether cyclized helical B peptide (CHBP). ARA290 and CHBP have promising applications as peptide drugs. The neuroprotective effects they exhibit have attracted continuous exploration of their mechanisms of action. This article will review the research on the role of EPO, ARA290 and CHBP in the nervous system around this developmental process, and provide a certain reference for the subsequent research.


Assuntos
Eritropoetina , Fármacos Neuroprotetores , Traumatismos dos Nervos Periféricos , Eritropoetina/uso terapêutico , Humanos , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Animais , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Peptídeos/uso terapêutico , Peptídeos/farmacologia , Oligopeptídeos
13.
Int J Biol Macromol ; 274(Pt 2): 133294, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38925188

RESUMO

Congenital heart disease (CHD) is a type of major defect that occurs during embryonic development. Although significant advances have been made in the treatment of CHD, its etiology and molecular mechanism remain unclear. To identify the critical role of SUMOylation in cardiac development, we generated SENP3 knockout mice and showed that SENP3 knockout mice die on embryonic day 8.5 with an open neural tube and reversed left-right cardiac asymmetry. Moreover, SENP3 knockout promoted apoptosis and senescence of H9C2 cells. Further studies showed that Nodal, a critical gene that forms left-right asymmetry, is regulated by SENP3 and that SENP3 regulates cell apoptosis and senescence in a Nodal-dependent manner. Furthermore, Nodal was hyper-SUMOylated after SENP3 knockout, and SUMOylation of Nodal inhibited its ubiquitination and ubiquitin-proteasome degradation pathway. Nodal overexpression enhanced cell apoptosis and senescence; however, the mutation at the SUMOylation site of Nodal reversed its effect on the apoptosis and senescence of H9C2 cells. More importantly, the SENP3-Nodal axis regulates cell senescence by inducing cell autophagy. These results suggest that the SENP3-Nodal signaling axis regulates cardiac senescence-autophagy homeostasis, which in turn affects cardiac development and results in the occurrence of CHD.


Assuntos
Apoptose , Cisteína Endopeptidases , Proteína Nodal , Transdução de Sinais , Sumoilação , Animais , Cisteína Endopeptidases/metabolismo , Cisteína Endopeptidases/genética , Camundongos , Apoptose/genética , Proteína Nodal/metabolismo , Proteína Nodal/genética , Coração/embriologia , Camundongos Knockout , Autofagia/genética , Senescência Celular/genética , Linhagem Celular
14.
Cell Mol Immunol ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38942796

RESUMO

Metabolic changes play a crucial role in determining the status and function of macrophages, but how lipid reprogramming in macrophages contributes to tumor progression is not yet fully understood. Here, we investigated the phenotype, contribution, and regulatory mechanisms of lipid droplet (LD)-laden macrophages (LLMs) in hepatocellular carcinoma (HCC). Enriched LLMs were found in tumor tissues and were associated with disease progression in HCC patients. The LLMs displayed immunosuppressive phenotypes (with extensive expression of TREM2, PD-L1, CD206, and CD163) and attenuated the antitumor activities of CD8+ T cells. Mechanistically, tumor-induced reshuffling of cellular lipids and TNFα-mediated uptake of tumoral fatty acids contribute to the generation of triglycerides and LDs in macrophages. LDs prolong LLM survival and promote CCL20 secretion, which further recruits CCR6+ Tregs to HCC tissue. Inhibiting LLM formation by targeting DGAT1 and DGAT2, which catalyze the synthesis of triglycerides, significantly reduced Treg recruitment, and delayed tumor growth in a mouse hepatic tumor model. Our results reveal the suppressive phenotypes and mechanisms of LLM enrichment in HCC and suggest the therapeutic potential of targeting LLMs for HCC patients.

15.
Clin Neurophysiol ; 164: 149-160, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38896932

RESUMO

OBJECTIVE: We aimed to determine whether quantitative electroencephalography (QEEG) measures have predictive value for cerebral edema (CED) and clinical outcomes in acute ischemic stroke (AIS) patients with anterior circulation large vessel occlusion who underwent mechanical thrombectomy (MT). METHODS: A total of 105 patients with AIS in the anterior circulation were enrolled in this prospective study. The occurrence and severity of CED were assessed through computed tomography conducted 24 h after MT. Clinical outcomes were evaluated based on early neurological deterioration (END) and 3-month functional status, as measured by the modified Rankin scale (mRS). Electroencephalography (EEG) recordings were performed 24 h after MT, and QEEG indices were calculated from the standard 16 electrodes and 2 frontal channels (F3-C3, F4-C4). The delta/alpha ratio (DAR), the (delta + theta) / (alpha + beta) ratio (DTABR), and relative delta power were averaged over all electrodes (global) and the F3-C3 and F4-C4 channels (frontal). The predictive effect and value of QEEG indices for CED and clinical outcomes were assessed using ordinal and logistic regression models, as well as receiver operating characteristic (ROC) curves. RESULTS: Significantly, both global and frontal DAR were found to be associated with the severity of CED, END, and poor functional outcomes at 90 days, while global and frontal DTABR and relative delta power were not associated with outcomes. In ROC analysis, the best predictive effect was observed in frontal DAR, with an area under the curve of approximately 0.80. It exhibited approximately 75% sensitivity and 71% specificity for radiological and clinical outcomes when a threshold of 3.3 was used. CONCLUSIONS: QEEG techniques may be considered an efficient bedside monitoring method for assessing treatment efficacy, identifying patients at higher risk of severe CED and END, and predicting long-term functional outcomes. SIGNIFICANCE: QEEG can help identify patients at risk of severe neurological complications that can impact long-term functional recovery in AIS patients who underwent MT.


Assuntos
Edema Encefálico , Eletroencefalografia , Trombectomia , Humanos , Masculino , Feminino , Idoso , Edema Encefálico/fisiopatologia , Edema Encefálico/diagnóstico por imagem , Edema Encefálico/etiologia , Pessoa de Meia-Idade , Trombectomia/métodos , Eletroencefalografia/métodos , Estudos Prospectivos , Ritmo Delta/fisiologia , Resultado do Tratamento , Ritmo alfa/fisiologia , AVC Isquêmico/fisiopatologia , AVC Isquêmico/cirurgia , Idoso de 80 Anos ou mais , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/cirurgia , Valor Preditivo dos Testes
16.
Immunology ; 173(1): 53-75, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38866391

RESUMO

The cross-regulation of immunity and metabolism is currently a research hotspot in life sciences and immunology. Metabolic immunology plays an important role in cutting-edge fields such as metabolic regulatory mechanisms in immune cell development and function, and metabolic targets and immune-related disease pathways. Protein post-translational modification (PTM) is a key epigenetic mechanism that regulates various biological processes and highlights metabolite functions. Currently, more than 400 PTM types have been identified to affect the functions of several proteins. Among these, metabolic PTMs, particularly various newly identified histone or non-histone acylation modifications, can effectively regulate various functions, processes and diseases of the immune system, as well as immune-related diseases. Thus, drugs aimed at targeted acylation modification can have substantial therapeutic potential in regulating immunity, indicating a new direction for further clinical translational research. This review summarises the characteristics and functions of seven novel lysine acylation modifications, including succinylation, S-palmitoylation, lactylation, crotonylation, 2-hydroxyisobutyrylation, ß-hydroxybutyrylation and malonylation, and their association with immunity, thereby providing valuable references for the diagnosis and treatment of immune disorders associated with new acylation modifications.


Assuntos
Processamento de Proteína Pós-Traducional , Humanos , Acilação , Animais , Imunidade , Doenças do Sistema Imunitário/imunologia , Doenças do Sistema Imunitário/metabolismo , Lisina/metabolismo
17.
Cancer Imaging ; 24(1): 62, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750551

RESUMO

OBJECTIVES: To develop and validate radiomics model based on computed tomography (CT) for preoperative prediction of CN0 status in patients with papillary thyroid carcinoma (PTC). METHODS: A total of 548 pathologically confirmed LNs (243 non-metastatic and 305 metastatic) two distinct hospitals were retrospectively assessed. A total of 396 radiomics features were extracted from arterial-phase CT images, where the strongest features containing the most predictive potential were further selected using the least absolute shrinkage and selection operator (LASSO) regression method. Delong test was used to compare the AUC values of training set, test sets and cN0 group. RESULTS: The Rad-score showed good discriminating performance with Area Under the ROC Curve (AUC) of 0.917(95% CI, 0.884 to 0.950), 0.892 (95% CI, 0.833 to 0.950) and 0.921 (95% CI, 868 to 0.973) in the training, internal validation cohort and external validation cohort, respectively. The test group of CN0 with a AUC of 0.892 (95% CI, 0.805 to 0.979). The accuracy was 85.4% (sensitivity = 81.3%; specificity = 88.9%) in the training cohort, 82.9% (sensitivity = 79.0%; specificity = 88.7%) in the internal validation cohort, 85.4% (sensitivity = 89.7%; specificity = 83.8%) in the external validation cohort, 86.7% (sensitivity = 83.8%; specificity = 91.3%) in the CN0 test group.The calibration curve demonstrated a significant Rad-score (P-value in H-L test > 0.05). The decision curve analysis indicated that the rad-score was clinically useful. CONCLUSIONS: Radiomics has shown great diagnostic potential to preoperatively predict the status of cN0 in PTC.


Assuntos
Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Tomografia Computadorizada por Raios X , Humanos , Feminino , Masculino , Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/patologia , Tomografia Computadorizada por Raios X/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Adulto , Idoso , Curva ROC , Adulto Jovem , Radiômica
18.
Nat Commun ; 15(1): 4535, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806516

RESUMO

Cryptophyte algae are an evolutionarily distinct and ecologically important group of photosynthetic unicellular eukaryotes. Photosystem II (PSII) of cryptophyte algae associates with alloxanthin chlorophyll a/c-binding proteins (ACPs) to act as the peripheral light-harvesting system, whose supramolecular organization is unknown. Here, we purify the PSII-ACPII supercomplex from a cryptophyte alga Chroomonas placoidea (C. placoidea), and analyze its structure at a resolution of 2.47 Å using cryo-electron microscopy. This structure reveals a dimeric organization of PSII-ACPII containing two PSII core monomers flanked by six symmetrically arranged ACPII subunits. The PSII core is conserved whereas the organization of ACPII subunits exhibits a distinct pattern, different from those observed so far in PSII of other algae and higher plants. Furthermore, we find a Chl a-binding antenna subunit, CCPII-S, which mediates interaction of ACPII with the PSII core. These results provide a structural basis for the assembly of antennas within the supercomplex and possible excitation energy transfer pathways in cryptophyte algal PSII, shedding light on the diversity of supramolecular organization of photosynthetic machinery.


Assuntos
Microscopia Crioeletrônica , Criptófitas , Complexo de Proteína do Fotossistema II , Complexo de Proteína do Fotossistema II/metabolismo , Complexo de Proteína do Fotossistema II/química , Criptófitas/metabolismo , Clorofila/metabolismo , Proteínas de Ligação à Clorofila/metabolismo , Proteínas de Ligação à Clorofila/química , Multimerização Proteica , Clorofila A/metabolismo , Clorofila A/química , Modelos Moleculares , Complexos de Proteínas Captadores de Luz/metabolismo , Complexos de Proteínas Captadores de Luz/química
19.
Anim Nutr ; 17: 376-386, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38812494

RESUMO

In markets for beef and sheep meat, an appropriate level of intramuscular fat (IMF) is highly desirable for meat-eating quality, but strategies to improve it usually lead to an undesirable excess in carcase fat, presenting a major challenge to livestock producers. To solve this problem, we need to understand the partitioning of fat among the major fat depots: IMF, subcutaneous fat (SCF) and visceral fat (VF). In most genotypes of cattle and sheep, the rate of accretion is lower for IMF than for SCF and VF, so genetic selection for a high level of IMF, or the use of an increased dietary energy supply to promote IMF deposition, will increase overall fatness and feed costs. On the other hand, feeding postnatal calves with excessive concentrates promotes IMF deposition, so a nutritional strategy is feasible. With genetic strategies, several problems arise: 1) positive genetic correlations between IMF, SCF and VF differ among genotypes in both cattle and sheep; 2) genotypes appear to have specific, characteristic rates of accretion of IMF during periods of growth and fattening; 3) most breeds of cattle and sheep naturally produce meat with relatively low levels of IMF, but IMF does vary substantially among individuals and breeds so progress is possible through accurate measurement of IMF. Therefore, an essential prerequisite for selection will be knowledge of the genetic correlations and fat accretion rates for each genotype. Currently, selection for IMF is based on existing technology that directly measures IMF in the progeny or siblings, or estimates IMF in live animals. New technology is needed to permit the simultaneous measurement of SCF and IMF in the field, thus opening up the possibility of accurate selection, particularly for fat partitioning in live animals. Specifically, there would be great value in detecting individuals with an IMF advantage at an early age so the generation interval could be shortened and genetic gain accelerated. Genetic gain would also be greatly aided if we could select for genes that control adipogenesis and lipogenesis and are also differentially expressed in the various depots.

20.
J Agric Food Chem ; 72(21): 12003-12013, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38748811

RESUMO

Insect gustatory receptors (GRs) aid in the precise identification of deterrent or stimulant compounds associated with food, mating, and egg-laying. Thus, they are promising targets for developing efficient insecticides. Here, 61 GRs in the chemosensory organs of Spodoptera litura larvae and adults were identified. Among them, SlitGR206 exhibited larval labium (LL)-specific expression characteristics. To explore the role of SlitGR206, a bacterial expression system was established to produce high-quality double-stranded RNA (dsRNA) and suppress SlitGR206 expression in LL. Subsequent behavioral assessments revealed that SlitGR206 silencing influenced larval feeding preferences and absorption. Moreover, it was found to reduce the ability of larvae to forage the five crucial host odorants. These findings demonstrate that SlitGR206 likely plays an indirect regulatory role in host recognition, consequently affecting foraging behavior. This provides a crucial foundation for the analysis of functional diversity among insect GRs and the precise development of nucleic acid pesticides in the future.


Assuntos
Comportamento Alimentar , Proteínas de Insetos , Larva , Spodoptera , Animais , Spodoptera/metabolismo , Spodoptera/fisiologia , Spodoptera/genética , Spodoptera/crescimento & desenvolvimento , Larva/metabolismo , Larva/crescimento & desenvolvimento , Larva/fisiologia , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Receptores de Superfície Celular/metabolismo , Receptores de Superfície Celular/genética
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